Practical Considerations and Survival Techniques for a Rat Model of Roux-En-Y Gastric Bypass
Drew a. Rideout*1,2, Steven S. Rakita2,1, Yanhua Peng2,3, William R. Gower2,3, Michel M. Murr1,2
1Department of Surgery, University of South Florida, Tampa, FL; 2Department of Surgery, James A. Haley Veterans Affairs Medical Center, Tampa, FL; 3Department of Molecular Medicine, University of South Florida, Tampa, FL
Background: A rat model for Roux-en-Y gastric bypass (RYGB) is associated with high operative mortality. We herein describe techniques to improve survival of obese rats that undergo RYGB.
Methods: Sprague-Dawley male rats were fed high fat diet for 14 weeks to induce obesity; subsequently obese rats underwent RYGB or sham operation. Despite following protocols published by others we continued to observe high rates of mortality in the immediate post-operative period. We, therefore, introduced a group of interventions aimed at improving survival after RYGB: 1) changed to inhalational anesthetic with streamlined operations to minimize anesthesia exposure (71±4min); 2) used metabolic cages peri-operatively to prevent rats from eating their bedding and feces; 3) modified the peri-operative diet with a 12 hour pre-operative fast and a gradual advance to full-strength Ensure post-operatively, followed by solid chow at 1 week; 4) created smaller gastric pouch and larger gastrojejunostomy to facilitate gastric emptying; 5) minimized handling and manipulation of the tissues. Weight and survival in the pre and post-intervention groups were compared.
Results: The first 8 rats were excluded to eliminate the confounding nature of the ‘technical’ learning curve. RYGB was undertaken in 18 rats done according to published protocols and in 21 rats after introducing our set of interventions. All deaths in the pre-intervention group were in the immediate 36 hours post-operatively (Table). Overall survival at 6 weeks post-operatively increased dramatically from 11% to 86% immediately after introducing our interventions. Obese rats who underwent sham operations (n=8) had similar overall survival (88%) as post-intervention RYGB rats. Survival was the same in all groups at the time of earliest tissue harvest for molecular studies (6 weeks). Body weight at 9 weeks was lower in RYGB rats compared to sham controls (364±45gm vs. 496±32gm; p<0.01).
Conclusion: RYGB is a technically challenging procedure in rodents; simple modifications in the operative conduct and peri-operative care of rats undergoing RYGB improve mortality in a predictable manner. Lessons learned from our experience will likely shorten the learning curve for researchers trying to establish animal models of obesity and RYGB.
| Operation<b/> | Survival 36 hours<b/> | Survival 6 weeks<b/> | |
| Pre-intervention (n=18)<b/> | RYGB | 11% | 11% |
| Post-intervention (n=21)<b/> | RYGB | 91% | 86% |
| Post-intervention (n=8)<b/> | Sham | 100% | 88% |
